Thymopoiesis is a complex process involving crosstalk between developing thymocytes and the non-hematopoietic stromal microenvironment, which includes thymic epithelial cells (TECs), fibroblasts and endothelial cells (ECs). Despite its importance, the thymus is exquisitely sensitive to damage caused by stress, infection, age, and cytoreductive treatments such as chemotherapy and radiation therapy. Continuous generation of adaptive immune diversity is dependent on T cell development in the thymus. However, despite this sensitivity to injury, the thymus also has extensive capacity for regeneration, although this does decline during aging.
Recent studies in tissues such as liver, lung and bone marrow have revealed that ECs not only passively deliver oxygen and nutrients to tissues, but also actively produce distinct paracrine factors that can orchestrate their repair. The role of thymic ECs in thymopoiesis beyond their contribution of local circulation and the importation of lymphoid progenitors has not been comprehensively studied.
There have been several strategies proposed for boosting thymus regeneration and recent discoveries have revealed pathways underlying endogenous regeneration. Although it is clear endothelial cells play a role in tissue regeneration, this has traditionally been attributed towards their role in vascularization, including in the thymus where EC production of VEGF is important during regeneration.
Thus the need exists for strategies to promote immune function, and offer therapies to boost thymic function